Various types of Hereditary Motor & Sensory Neuropathy (HMSN) are common causes of neurologic disability and death for which improved understanding of natural history, pathophysiology of symptoms and a cellular and molecular explanation for fiber degeneration and improved approaches to treatment are sought. Specifically in the new disorder Multneuronal Degeneration plus we seek to characterize the compositional and structural abnormalities of lipids of various tissues. Next we will attempt to localize the metabolic block of the w6 series of polyenoic fatty acid pathway and of fatty acid oxidation by modification of dietary intake and by in vitro incorporation of radiolabeled precursors into isolated blood elements and cultured fibroblasts. Insights gained will be used in neurologically monitored clinical trials. In more common types of HMSN our extensive past evaluation of both affected and unaffected persons from kinships, studied extensively by in vivo and in vitro electrophysiologic approaches, by unique computer assisted systems to estimate detection threshold of sensation and by pathologic and morphometric studies of nerve will now be abstracted and compared to gain a better understanding of natural history, pathophysiology of symptoms and risk by graded neurologic disability by decade. Extensive pathologic and morphometric studies of biopsied sural nerves are planned to assess: 1. The population and level of neuron pathology; 2. Whether axonal atrophyleads sequentially to myelin wrinkling, to nodal lengthening & segmental demyelination, to remyelination (& development of onion bulb formation) & fiber loss; 3. Wheter neurofliament decrease, increase or midsirection plays a role in axonal pathology; 4. The cellular responsibility for hypomyelination & segmental demyelination using xenografted nerve; 5. The demyelinating activity (& components) of serum when endoneurially injected; & 6. The chemical composition of lipids, apoproteins & carbohydrate moieties of endoneurium & endoneurial fluid to recognize altered composition & metabolism which could alter nerve function & environment & play a role in fiber degeneration & recovery.